37, 738748 (2009). Predominant cellular mitochondrial dysfunction in the TOP3A gene-caused Bloom syndrome-like disorder. Commun. 1; Supplementary Fig. Analysis of t(15;17) chromosomal breakpoint sequences in therapy-related versus de novo acute promyelocytic leukemia: association of DNA breaks with specific DNA motifs at PML and RARA loci. Finally, the detailed location and roles of topoisomerases at centromeres and telomeres, and how topoisomerases are coordinated with chromatin remodelling factors and the architecture of chromatin and chromosomes, represent promising areas of investigation. At the end of S phase, in addition to its role in resolving ultra-fine DNA bridges between sister chromatids52, TOP3A in coordination with the helicase Plk1-interacting checkpoint helicase (PICH; also known as ERCC6L) has been shown to generate replicated DNA Sc+ segments, which are preferential substrates for TOP2A-mediated decatenation, thereby enabling the segregation of chromatin fibres during anaphase53. Roles of topoisomerases in nuclear organization and genomic stability. Sekiguchi, J., Seeman, N. C. & Shuman, S. Resolution of Holliday junctions by eukaryotic DNA topoisomerase I. Proc. 1f,g). Unlike type IA topoisomerases (TOP3A and TOP3B) (see below), TOP1 and TOP1MT only process double-stranded DNA and relax DNA supercoils processively and without metal or protein cofactor by controlled rotation of the broken strand around the intact strand20,21, with a preference for nucleosome-free DNA10,22 (Supplementary Fig. Biol. 264, 97139715 (1989). Crit. Verver, D. E. et al. Recent analyses in human B cells show that more than 90% of TOP1-DPCs are removed during a 15-min repair time in wild type and TDP2/ cells, 70% in TDP1/ cells and only 40% in TDP1/TDP2/ cells253. Capranico, G., Jaxel, C., Roberge, M., Kohn, K. W. & Pommier, Y. Nucleosome positioning as a critical determinant for the DNA cleavage sites of mammalian DNA topoisomerase II in reconstituted simian virus 40 chromatin. DNA Repair 94, 102926 (2020). Biochim. PubMed Central Cell 1, 741748 (1998). The BTR dissolvasome complex has been shown to sense replication protein A (RPA)-coated single-stranded DNA, which may explain its role in restarting stalled replication forks50,51. Chapman, J., Ng, Y. S. & Nicholls, T. J. APE2 promotes DNA damage response pathway from a single-strand break. Liu, L. F. & Wang, J. C. Supercoiling of the DNA template during transcription. Following hydrolysis of the 5-tyrosyl bond by TDP2 (Tdp1 in yeast), gap filling by DNA polymerase generates a blunt-ended DSB, which is ligated by NHEJ. Clin. When CTCF sites are convergent, the C termini of their bound CTCFs are positioned to interact with the cohesins at TAD borders57 (Fig. Hum. Cell Biol. Enzymes called helicases then separate the two strands of the double helix, exposing two template surfaces for the alignment of free nucleotides. 14, 83918398 (1994). 307, 301307 (2003). H2AX and cancer. 27, 14051406 (2017). 10, 87 (2019). B. et al. Yang, X., Li, W., Prescott, E. D., Burden, S. J. 3, 733 (2012). e | TOP3A in association with the Bloom syndrome protein (BLM)TOP3ARecQ-mediated genome instability proteins (RMI1/2) (BTR) dissolvasome complex (not shown) resolves DNA hemicatenanes arising during replication and recombination by passing a single strand of DNA through a break made in another DNA strand (single-strand passage)6,357. f | TOP3B is the only RNA-only topoisomerase14; it resolves intramolecular RNA intertwines (knots) by single-strand passage. 293, 1052410535 (2018). Platinated DNA adducts enhance poisoning of DNA topoisomerase I by camptothecin. Enforced cytokinesis without complete nuclear division in embryonic cells depleting the activity of DNA topoisomerase II. Nature 434, 108113 (2005). Topoisomerase enzymes cut, uncoil and reseal the double stranded DNA 2. 45, 45644576 (2017). The 3 ends of the break can undergo resection followed by gap filling. DNA gyrase: structure and function - PubMed Association with Aurora-A controls N-MYC-dependent promoter escape and pause release of RNA polymerase II during the cell cycle. Such seDSBs are highly cytotoxic204, unless the replication fork reverses (Fig. Natl Acad. Waldman, T. Emerging themes in cohesin cancer biology. Article [55] Topo II and PARP-1 increased at the site of the double-strand break and components of the non-homologous end joining DNA repair pathway, including DNA-PKcs, Ku70/Ku80 and DNA ligase IV assembled with topo II and PARP-1. Li, T. K. et al. 1) until the torsional strain is eliminated. Topoisomerase III is required for normal proliferation and telomere stability in alternative lengthening of telomeres. Human mitochondrial topoisomerase I. Proc. Another duplex, termed the transport segment (T-segment), is captured by an ATP-operated clamp and passed through a transient break in the G-segment, involving 5 phosphotyrosine linkages in both strands, before it is released through the C-gate and the G-segment is re-ligated (Fig. It refers to the number of times the two strands of the duplex make a complete 360 degree turn. Model for MLL translocations in therapy-related leukemia involving topoisomerase II-mediated DNA strand breaks and gene proximity. If the TOPccs fail to reseal, they become topoisomerase DNAprotein crosslinks (TOP-DPCs): stalled (abortive or irreversible) TOPccs consisting of a DNAprotein (topoisomerase) crosslink at the end of a break, which require DNA repair for their resolution (see below). PubMed Being a highly processive swivelase, TOP1 can remove supercoils in short DNA segments devoid of nucleosomes, whereas TOP2A, acting as a writhase, likely acts at crossover points where the DNA enters and exits nucleosomes22,38 (Fig. Mol. Stigler, J., Camdere, G. O., Koshland, D. E. & Greene, E. C. Single-molecule imaging reveals a collapsed conformational state for DNA-bound cohesin. Similar to the complete loss of MRE11, neuron-specific disruption of Nijmegen breakage syndrome 1 (NBS1), an essential cofactor of MRE11 (with RAD50), also causes the accumulation of endogenous TOP2cc242. Sordet, O. et al. 195, 739749 (2011). TOP3A, in addition to its roles in resolving double Holliday junctions and suppressing sister chromatid exchanges, is involved in DNA end resection160 and homology-directed repair (HDR)6,28,161,162. 12, e1006483 (2016). Nitiss, K. C., Malik, M., He, X., White, S. W. & Nitiss, J. L. Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage. DNA Repair. Blood 115, 326330 (2010). Davies, S. L., North, P. S. & Hickson, I. D. Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Therapy-associated AML appearing after exposure to TOP2 poisons often contains one of a set of recurrent chromosomal translocations giving rise to fusion genes that disrupt blood cell development and differentiation17,228,295. Topoisomerase 1 (TOP1), mitochondrial TOP1 (TOP1MT), TOP2A and TOP2B remove both Sc+ and Sc by incising double-stranded DNA; TOP3B (and TOP3A) relax hyper-negative supercoiling by nicking and closing single-stranded DNA segments. 6; Supplementary Fig. Proc. Martin, C. A. et al. (TDPs). & El-Khamisy, S. F. ATM deficiency results in accumulation of DNAtopoisomerase I covalent intermediates in neural cells. J. Biol. USA 119, e2114024119, (2022). Drug Metab. & Kaufmann, S. H. Topoisomerases and cancer chemotherapy: recent advances and unanswered questions. Induction of apoptosis by depletion of DNA topoisomerase II in mammalian cells. Kim, R. A. Proc. Nature 518, 409412 (2015). 7), originally derived from the tree Camptotheca acuminata, targets human topo I and derivatives such as topotecan and irinotecan are widely used in cancer chemotherapy. However, it is not known whether the potential role of TOP3B in resolving R-loops is related to its dual DNA and RNA topoisomerase activities. Transcriptional elongation requires DNA break-induced signalling. 1g,h). Nat. 1, 417424 (1995). a | Model for formation of topoisomerase 1 (TOP1)-mediated deletions at sites of ribonucleotide incorporation within short tandem repeats. 280, 35643573 (2005). 27, 16781691 (2013). Topoisomerase: Overview & Applications - Excedr Vian, L. et al. Mol. In mitochondria, TOP3A acts as a hemicatenane resolvase; in its absence, newly replicated mtDNA molecules remain intertwined at the mtDNA replication origin, a phenotype which is further accentuated in the absence of TOP1MT.12 (Box1). Acad. Pommier, Y. Natl Acad. Chiang, S.-C. et al. Sasanuma, H. et al. Chem. Mol. Cell 75, 203205 (2019). In contrast to the dominant role for HDR in repairing TOP1-induced DSBs, NHEJ is preferentially used for TOP2-induced DSBs even in cycling cells222 (Fig. Replication fork regression induced by poly(ADP-ribose) polymerase 1 (PARP1)363 promotes TOP1cc self-reversal or fork stabilization and replication restart with RAD51 and breast cancer-associated type 2 (BRCA2). 2a,b). (In supercoiling the DNA molecule coils up like a telephone cord, which shortens the molecule.) Reijns, M. A. et al. Gemcitabine (2,2-difluoro-2-deoxycytidine), an antimetabolite that poisons topoisomerase I. Clin. Ahmad, M., Xu, D. & Wang, W. Type IA topoisomerases can be magicians for both DNA and RNA in all domains of life. Blood 117, 21372145 (2011). Natl Acad. After the signal occurred, topo II caused a double-strand break and PARP-1 was involved in replacing histone H1 by HMGB1/HMGA2, which can promote transcription. Rev. Bonner, W. M. et al. Science 332, 15611564 (2011). Rajapakse, V. N. et al. Eur. This prior review complements the current Review with detailed biochemical and pharmacological information. Bidirectionalreplication and transcription of mtDNA represent model systems for DNA supercoiling, R-loops, G quadruplexes and decatenation. Rialdi, A. et al. Conversion of topoisomerase I cleavage complexes on the leading strand of ribosomal DNA into 5-phosphorylated DNA double-strand breaks by replication runoff. Get the most important science stories of the day, free in your inbox. Nat. The 3 parameters are related as follows: Lk = Tw +Wr. Champoux, J. J. DNA topoisomerases: structure, function, and mechanism. Nature 501, 5862 (2013). Pouliot, J. J., Robertson, C. A. Which topoisomerase is relevant in DNA replication? [47] However, dexrazoxane, which blocks ATP hydrolysis by topo II, is used to prevent cardiotoxicity associated with the anthracyclines. Cell Res. DNA topoisomerase I differentially modulates R-loops across the human genome. Nature Reviews Molecular Cell Biology A. M. et al. DNA topoisomerases are important targets of . Mol. Human topoisomerases and the associated repair enzymes tyrosyl-DNA phosphodiesterases (TDPs; TDP1 and TDP2) are located both in the nucleus and in mitochondria; in addition, cytoplasmic RNAs are handled by TOP3B and TDP2 (refs1,2) (Supplementary Table 1). Notably, TOP1MT is transcriptionally activated by the oncogene MYC178. Wu, L. & Hickson, I. D. The Blooms syndrome helicase suppresses crossing over during homologous recombination. Piskadlo, E. & Oliveira, R. A. Adv. Kwan, K. Y. et al. Nature 461, 674678 (2009). 1a,b). This work presents the first evidence for cellular TOP3B RNA cleavage complexes and repair pathways. TOP1 has recently been shown to bind the heptad repeats of the Pol II CTD in association with the chromatin regulator bromodomain-containing protein 4 (BRD4)56 (Fig. Non-proteolytic pathway for TOP2, driven by SUMO E3 ligase ZNF451 (ref.259) (step 3). 2023 Sizzling Summer Science Spotlight ( S4 ) series begins 276, 4065240658 (2001). Sci. HSP-90 inhibitor ganetespib is synergistic with doxorubicin in small cell lung cancer. CAS TOP2B: the first thirty years. J. Mol. & Wang, J. C. Infertility and aneuploidy in mice lacking a type IA DNA topoisomerase III. Maede, Y. et al. Cytogenet. International workshop on the relationship of prior therapy to balanced chromosome aberrations in therapy-related myelodysplastic syndromes and acute leukemia: overview report. Topoisomerase 1-mediated removal of ribonucleotides from nascent leading-strand DNA. Clin. Nucleic Acids Res. Acta 1400, 233255 (1998). 3, e1602506 (2017). In this Review we have discussed the emerging range of (redundant) repair pathways that handle the failures of topoisomerases in physiological conditions and following their therapeutic targeting. However, error-prone NHEJ frequently occurs in camptothecin-treated cells upon inhibition of ATM226,277, suggesting that genome instability resulting from endogenous TOP1cc is accentuated in the context of ATM and HDR deficiencies. [6] DNA gyrase catalyzes the introduction of negative supercoils into DNA and is the only type II enzyme to do this, all the others catalyze DNA relaxation. Sci. Thus, HSP90 appears to be required for maintaining the conformation of TOP2 and avoiding TOP2 misfolding and the stalling of TOP2-DPCs. Both TDP2 and MRE11 remove TOP2 adducts (Fig. Sci. & Hammarsten, O. Pourquier, P. et al. Google Scholar. Increased negative supercoiling of mtDNA in TOP1mt knockout mice and presence of topoisomerases II and II in vertebrate mitochondria. Sc, supercoiling. Am. Gangloff, S., MacDonald, J. P., Bendixen, C., Arthur, L. & Rothstein, R. The yeast type 1 topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. J. Immunol. Karras, G. I. et al. Sci. Oncogene 33, 48674876 (2014). 11, 1318 (2020). Genet. https://doi.org/10.1038/s41586-022-04403-y, DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence, Replication-associated formation and repair of human topoisomerase III cleavage complexes, Regulation of biological processes by intrinsically chiral engineered materials, Pectolinarigenin inhibits bladder urothelial carcinoma cell proliferation by regulating DNA damage/autophagy pathways, Super-resolution microscopy reveals the number and distribution of topoisomerase II and CENH3 molecules within barley metaphase chromosomes, Cancel TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. Induction of topoisomerase I cleavage complexes by 1--d-arabinofuranosylcytosine (ara-C) in vitro and in ara-C-treated cells. This work was also supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (16H12595 and 16H06306) (to S.T.) & Roca, J. Topoisomerase II, not topoisomerase I, is the proficient relaxase of nucleosomal DNA. Cristini, A. et al. & Wang, J. C. Mice lacking DNA topoisomerase III develop to maturity but show a reduced mean lifespan. 3). & Baxter, J. This article provides evidence for the selective activity of yeast TOP2 positive supercoils using single-molecule techniques. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Topoisomerase - an overview | ScienceDirect Topics 1c). Nat. 2a) appears to be less efficiently processed. 1.6: DNA Supercoiling and Topoisomerases - Biology LibreTexts The first DNA topoisomerase was discovered in bacteria by James Wang in 1971 and was initially named (omega) protein;[3] it is now called Escherichia coli (E. coli) topoisomerase I (topo I) and is a representative of the type IA family of enzymes. Cell 25, 663675 (2007). 17, 207223 (2016). Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2). In molecular biology Type I topoisomerases are enzymes that cut one of the two strands of double-stranded DNA, relax the strand, and reanneal the strand. Mol. This work presents a detailed overview of the type I topoisomerases, which complements the present Review. J. Biol. Commun. What is the role of topoisomerase Why is this necessary? Biol. Chem. This work establishes that there is an innate link between DNA cleavage predisposition and sensitivity to topoisomerase II poisons, and that certain sequence variants of human type II topoisomerases found in cancer cells can act as DNA-damaging agents. Google Scholar. Because topoisomerases are exploited as targets for a wide range of anticancer and antibacterial drugs, understanding the repair pathways of TOPccs can provide opportunities for improving the rational use of topoisomerase inhibitors and their combination with other drugs in cancer treatment. Involved in RNA processing, Removes (-), but not (+) supercoils, introduces positive supercoils, Removes (+) and (-) supercoils; supports fork movement during replication and transcription. lvarez-Quiln, A. et al. Topoisomerase I-driven repair of UV-induced damage in NER-deficient cells. DNA topoisomerases are the magicians of the DNA world by allowing DNA strands or double helices to pass through each other, they can solve all of the topological problems of DNA in replication, transcription and other cellular transactions. Synergistic coordination of chromatin torsional mechanics and topoisomerase activity. Crit. PLoS ONE 4, e5859 (2009). The endogenous accumulation of TOP1-DPCs has been detected in mice deficient in the kinase ATM or in the protease Spartan (SPRTN)247,250. DNA topoisomerases: structure, function, and mechanism Desai, S. D., Liu, L. F., Vazquez-Abad, D. & DArpa, P. Ubiquitin-dependent destruction of topoisomerase I is stimulated by the antitumor drug camptothecin. Each human mitochondrial DNA (mtDNA) molecule consists of circular DNA of 16,569bp assembled in a nucleoid, which is tethered to the inner mitochondrial membrane338,367 Replication of the G-rich heavy strand originates from the OriH sequence in the ~1kb non-coding region. Evidence for an intermediate with a single-strand break in the reaction catalyzed by the DNA untwisting enzyme. Other topological difficulties arise during replication and chromatin loop formation when duplex DNA molecules form catenanes. Nature Reviews Molecular Cell Biology thanks the anonymous reviewers for their contribution to the peer review of this work. The G segment is part of a much longer piece of DNA (>100 bp) that is wrapped around the enzyme, one arm of which forms the T-segment that is passed through the double-stranded break (Fig. Recruitment of TOP3B by Tudor domain-containing protein 3 (TDRD3), which interacts with the Pol II CTD, suppresses R-loops27. Somatic mutations in tumours may also provide therapeutic opportunities related to synthetic lethality, such as the use of PARP inhibitors to block the TDP1 repair pathway in ERCC1-deficient cancers treated with TOP1 inhibitors275 (Fig. J. Biochem. Natl Acad. a | Transcription induces positive DNA supercoiling (Sc+) ahead of RNA polymerase II (Pol II) and negative supercoiling (Sc) behind it54. Topoisomerases and the regulation of neural function Chem. Misteli, T. The self-organizing genome: principles of genome architecture and function. Based on these data, a model was proposed in which TOP1 is recruited to promoters, but kept inactive until phosphorylation of Pol II CTD Ser2 by BRD4 releases Pol II and TOP1 from promoter-proximal pausing into productive transcript elongation56. c | TOP2A and TOP2B decatenate topological domains by passing one DNA molecule through the double-stranded DNA break made in the other DNA molecule (double-strand passage). USA 82, 31243128 (1985). Canela, A. et al. Biol. 19, 13241334 (2010). 89, 102837 (2020). Proc. Lam, C. W., Yeung, W. L. & Law, C. Y. Clinically successful topoisomerase-targeting anticancer drugs act through topoisomerase poisoning, which leads to replication fork arrest and double-strand break formation. Position-specific effects of base mismatch on mammalian topoisomerase II DNA cleaving activity. PubMed Husain, A. et al. Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Kim, N. et al. USA 117, 1441214420 (2020). d | TOP2A and TOP2B resolve DNA knots by double-strand passage. Hasan, S. K. et al. 5a). Sci. Rosa, I. D., Zhang, H., Khiati, S., Wu, X. [10] Potential topological issues associated with the double-helical structure of DNA were recognized soon after its structure was first elucidated in 1953 by James Watson, Francis Crick and Rosalind Franklin[11][12][13] and developed further by the work of Max Delbruck and John Cairns. & Pommier, Y. Topoisomerase I-mediated cleavage at unrepaired ribonucleotides generates DNA double-strand breaks. Commun. USA 86, 34893493 (1989). 3h,i). 2, 209214 (1991). TOP2A may minimize DNA entanglements as condensin organizes mitotic DNA loops9,118,119,120,121. Ho, J. S. Y. et al. In the case of gyrase, a substantial amount of the free energy from ATP hydrolysis is transduced into torsional stress in DNA, i.e. Mol. Natl Acad. Targeting DNA topoisomerase II in cancer chemotherapy - Nature Takashima, H. et al. Anticancer drugs targeting TOP2 enzymes (Supplementary Box 1) are associated with long-term undesirable side effects including therapy-related acute myeloid leukaemia (t-AML)17,286,287. Beyond the unwinding: role of TOP1MT in mitochondrial translation. t-AML occurs following treatment for a wide range of primary neoplasia. However, similar to the majority of mitochondrial proteins, they do not bear identifiable mitochondrial targeting sequences. The 5 end of DNA is captured by TOP1, which is followed by rejoining of the two ends and release of TOP1, thus generating a short deletion144,151,152. These drugs are classically used to map TOP2ccs and study their DNA damaging effects and repair pathways32,48,206,227,228,229,230. It is likely that the sites of damage and whether topoisomerases are trapped during transcription or replication, or whether the damage occurs in highly proliferative cells such as haematopoietic progenitors or in highly differentiated cells such as neurons, are germane to repair pathway choice. They are also grateful to the three reviewers who provided multiple suggestions and careful corrections. 19, 114129 (2014). 1. 20, 387395 (2013). Topoisomerase Overview & Function | What is Topoisomerase? - Video DNA catenanes are formed upon the replication of circular molecules and need to be resolved by topoisomerases or recombinases to allow proper separation of daughter molecules during cell division. However, yeast Top2 has recently been shown to promote sister chromatid intertwines during prophase while removing them at the onset of anaphase122. Transcription 7, 7583 (2016). Rev. Imai, H. et al. J. Mol. In this Review, we first provide basic information on the six human topoisomerases. Cell Res. 1c). R-loops forming due to insufficient TOP1 activity induce DSBs (bottom)72. d | Insufficient topoisomerase activity can result in excessive positive DNA supercoiling (Sc+) that arrests transcription and replication, and in negative supercoiling (Sc) that induces formation of R-loops and alternative DNA structures, including G quadruplexes (G4) and Z-DNA67,165. In addition to the detrimental aspects of DNA topology that require resolution, there are also beneficial aspects. Exposure to etoposide either at an elevated temperature (39C) or together with an inhibitor of heat shock protein 90 (HSP90) enhances the abundance of TOP2-DPCs233,234. 61, 716729 (2020). Gravel, S., Chapman, J. R., Magill, C. & Jackson, S. P. DNA helicases Sgs1 and BLM promote DNA double-strand break resection. Genes 10, 868 (2019). A plausible role for DNA topoisomerase II in carcinogenesis, for example, has been proposed 96. Reijns, M. A. M. et al. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in If the replisome swivels due to the twisting force, Sc+ diffuses behind the replisome and generates precatenanes, which are removed by TOP2A37. DNA topoisomerase II in therapy-related acute promyelocytic leukemia. Struct. Huang, S. N., Williams, J. S., Arana, M. E., Kunkel, T. A. Both human topo I and topo II (both and isoforms) can be targeted in anticancer chemotherapy (Fig. Cell. Cell Rep. 33, 108569 (2020). Loop extrusion as a mechanism for formation of DNA damage repair foci. Sci. The cerebral cortex develops normally, but neurons exhibit reduced transcription of long genes and, ultimately, undergo degeneration at postnatal day7, which is accompanied by accumulation of the DNA damage response biomarker H2AX167. Nature 497, 624627 (2013). [14][15] Closed-circular double-stranded DNA can be described by 3 parameters: Linking number (Lk), Twist (Tw) and Writhe (Wr) (Fig. Although these proteins are not viable as antibacterials, their mode of action could inspire the development of novel antibacterial compounds. Rev. 47, 29062921 (2019). Chromosome break points involved in MLL translocations in AML fall within an 8kb break-point cluster region, and those derived from t-AML are over-represented in the distal 1kb of this break-point cluster region. EMBO Rep. 21, e49367 (2020). Mauritzson, N. et al. Distribution bias and biochemical characterization of TOP1MT single nucleotide variants. Biochemistry 40, 33163323 (2001). Nucleic Acids Res. Sci. Type IIA topoisomerases allow DNA double helical strands to pass through each other by generating transient DNA double strand breaks DSBs), and in so doing, resolve torsional strain that accumulates during transcription, DNA replication, chromosome condensation, chromosome segregation and . Stalled or irreversible TOP2Bccs generate DSBs that disjoin the loops. Nucleic Acids Res. 157, 128131 (2012). Conversely, DNA is negatively supercoiled if Lk of the molecule is lower than the Lk0 (Lk<0). DNA Repair. Dev. Nat. 4). J. 44, 28162826 (2016). This assemblage was all present at the linker DNA adjacent to a single nucleosome in the promoter region of a gene (see Figure). Ishida, R. et al. Manville, C. M. et al. Pourquier, P. et al. This article provides evidence and a model for the role of TOP1 and BRD4 in transcription regulation. Cell 47, 980986 (2012). Blood 87, 26492658 (1996). Nat. BAZ2A safeguards genome architecture of ground-state pluripotent stem cells. Nature 442, 818822 (2006). PICH and TOP3A cooperate to induce positive DNA supercoiling. Kim, N. & Jinks-Robertson, S. The Top1 paradox: friend and foe of the eukaryotic genome. Open. [25] This is followed by ligation of the G-segment. 55, 509524 (2020). c | TOP2-mediated short duplications203. [21] These topological perturbations must be resolved for DNA metabolism to proceed, allowing the cell to efficiently replicate, transcribe and partition the genome to enable cellular division and vitality. Trapped TOP1ccs are a well-established source of mutations and genomic instability (Figs 4,5). As pointed out by Singh et al.,[58] "about 80% of highly expressed genes in HeLa cells are paused". Cell. Unlike TOP1, TOP1MT is dispensable for mouse development173 (Table1). This article uses End-seq to map TOP2 sites with cohesin and CTCF. Lack of mitochondrial topoisomerase I (TOP1mt) impairs liver regeneration. Sen, N. et al. 6). This process changes the linking number of the DNA by +/-2. Zhang, H., Meng, L. H., Zimonjic, D. B., Popescu, N. C. & Pommier, Y. Thirteen-exon-motif signature for vertebrate nuclear and mitochondrial type IB topoisomerases. Nat. Bedez, C. et al. Topoisomerases bind to DNA in a noncovalent fashion followed by the formation of transient cleavage complexes. Commun. [24] The gene encoding reverse gyrase is also found in some groups of thermophilic bacteria, where it was likely transferred by horizontal gene transfer from Archaea.[26]. Role of topoisomerase in transcriptional regulation, World Health Organization's List of Essential Medicines, "Diversity and Functions of Type II Topoisomerases", "An activity from mammalian cells that untwists superhelical DNA--a possible swivel for DNA replication (polyoma-ethidium bromide-mouse-embryo cells-dye binding assay)", "DNA gyrase: an enzyme that introduces superhelical turns into DNA", "Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme", "T4 DNA-delay proteins, required for specific DNA replication, form a complex that has ATP-dependent DNA topoisomerase activity", "On the Replication of Desoxyribonucleic Acid (Dna)", "Topological challenges to DNA replication: conformations at the fork", "Supercoiling of the DNA template during transcription", "The Stringent Response Inhibits DNA Replication Initiation in E. coli by Modulating Supercoiling of, "Widespread distribution of archaeal reverse gyrase in thermophilic bacteria suggests a complex history of vertical inheritance and lateral gene transfers", "Structural studies of type I topoisomerases", "The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaks", "Topoisomerase VI is a chirally-selective, preferential DNA decatenase", "Drugging topoisomerases: lessons and challenges", "DNA topoisomerases and their poisoning by anticancer and antibacterial drugs", "Interfacial inhibitors: targeting macromolecular complexes", "Targeting bacterial topoisomerase I to meet the challenge of finding new antibiotics", "Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance", "The Microbial Toxin Microcin B17: Prospects for the Development of New Antibacterial Agents", "A strand-passage conformation of DNA gyrase is required to allow the bacterial toxin, CcdB, to access its binding site", "Direct control of type IIA topoisomerase activity by a chromosomally encoded regulatory protein", "The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic", "Pentapeptide repeat protein QnrB1 requires ATP hydrolysis to rejuvenate poisoned gyrase complexes", "Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide", "Topoisomerase II Poisons: Converting Essential Enzymes into Molecular Scissors", "The indenoisoquinoline noncamptothecin topoisomerase I inhibitors: update and perspectives", "Emerging themes in neuronal activity-dependent gene expression", "BRCA1-BARD1 regulates transcription through modulating topoisomerase II", "A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome", "Pausing sites of RNA polymerase II on actively transcribed genes are enriched in DNA double-stranded breaks", "A role of DNA-PK for the metabolic gene regulation in response to insulin", "Transcriptional elongation requires DNA break-induced signalling", "Glucocorticoid Receptor Transcriptional Activation via the BRG1-Dependent Recruitment of TOP2 and Ku70/86", "Profiling DNA break sites and transcriptional changes in response to contextual fear learning", https://en.wikipedia.org/w/index.php?title=Topoisomerase&oldid=1142251510, Removes (-), but not (+) supercoils.